Management of Diastolic Heart Failure:
What is the Recent Results in Clinical Trial
報告學生:陳秋縈
指導老師:李貽恆醫師
報告日期:2012/11/13
CA...
2
Patient profile
Name 吳○○ Admission date 2012/10/18
Age 79 Allergy history NKDA
Gender female Social history Smoking: (-)...
3
History of present illness
• Intermittent exertional dyspnea for several years
• Long term follow up in local clinic
4/1...
4
Physical examination
• VITAL SIGN
TPR: 37.7/85/20 BP: 141/78 mmHg SpO2: 92%
• NECK: JVE(+)
• CHEST: crackles over right ...
5
Lab data
Impression
• HF with AE, favor infection induced
• Af with RVR
• HTN
Normal
range
10/18
ALBUMIN 3.5-5 4.1 g/dL
...
6
Hospital course
Date Event Management
10/18
16:00
at ER
• BT: 37.7, cough, dyspnea
• CXR : patchy consolidatoins and inf...
7
Date Event Management
10/18
18:00
after
admission
HF with AE, favor infection related
HTN previous under amlodipine
• Sc...
8
Date Event Management
10/21 • Keep Valsartan use
10/22 • SOB improved, no orthopnea,
less cough, less edema
• F/U lab no...
9
Summary of our patient
Drug 10/18 10/19 10/20 10/21 10/22 10/23
discharge
order
CAP
Ceftriaxone 100mg IVD q12h
Levofloxa...
10
Outline
 Diastolic heart failure (DHF)
 Definition and diagnosis criteria
 Epidemiology
 Pathophysiology
 Clinical...
11
Heart failure
 A complex clinical syndrome that can result from any
structural or functional cardiac disorder that imp...
Diastolic Heart Failure (DHF)
Also called:
• Diastolic dysfunction
• Heart failure with preserved ejection fraction (HFPEF...
13
Definition
 Vary with no global consensus
 A clinical syndrome
 Signs or symptoms of heart failure
 Congestion, low...
14
Diagnostic Criteria
Adapted from Yturralde FR. Prog Cardiovasc Dis 2005;47:314-19
2009 Focused Update: ACCF/AHA Heart F...
15
Epidemiology
 50% of patients with HF has normal LVEF
 Increasing prevalence
Secular Trends in the Prevalence of HF-P...
16
Mortality: SHF vs. DHF
 Varies with cohort studied
 Differences in definition used to diagnose, co-morbidities
presen...
17
Patient Characteristics: SHF vs. DHF
Owan T, et al. NEJM. 2006;355:251-9
older
female





lower
SHF DHF
18
Etiology
Major causes
 Hypertension
 Coronary heart disease
 Diabetes
 Cardiomyopathy
Precipitating factors
 Exces...
19
Pathophysiology
Mandinov L, Eberli FR, Seiler C, Hess OM. Cardiovasc Res. 2000 Mar;45(4):813-25.
Abnormalities of activ...
20
Clinical Manifestations
Extravascular water ↑
 Dyspnea
 Elevated jugular venous
pressure
 Pulmonary rales
 Edema
Ti...
21
Management
 Limited evidence, no standard treatment regimen
Hunt, et al. 2009 ACCF/AHA Heart Failure Guidelines. Circu...
22
Goal
• Control hypertension
• Reduce the congestive state
• Treat and prevent myocardial ischemia
• Maintain atrial con...
23
SHF vs. DHF
Systolic heart failure Diastolic heart failure
Pathophysiology
Impaired myocardial contractility
Dilated he...
What is the recent results in
clinical trial
25
Completed trials for HF with preserved EF
Trial Drug Patient Follow-up
PEP-CHF
2006
Perindopril
•n=850
•EF ≥ 40%
26.2 m...
26
PEP-CHF: Perindopril
Perindopril in Elderly People with Chronic Heart Failure
Eur Heart J. 2006 Oct;27(19):2338-45
Pati...
27
PEP-CHF: Perindopril
Cleland JG, Tendera M, Adamus J, et al. Eur Heart J. 2006 Oct;27(19):2338-45.
Results
Perindopril ...
28
VALIDD (Valsartan in Diastolic Dysfunction)
Effect of angiotensin receptor blockade and antihypertensive drugs on diast...
29
I-PRESERVE: Irbesartan
Irbesartan in patients with heart failure and preserved ejection fraction
N Engl J Med. 2008 Dec...
30
CHARM-Preserved: Candesartan
Effects of candesartan in patients with chronic heart failure and preserved left-
ventricu...
31
Results
Candesartan vs. Placebo
•Reduce hospital admission for HF
15.9% vs. 18.3% (p=0.047, NNT 42)
•Cardiovascular dea...
32
Angiotensin receptor blockers for heart failure
Cochrane Database Syst Rev. 2012 Apr 18;4:CD003040.
 Study design: Sys...
33
Total Mortality
Total Hospitalizations
ARBs vs. placebo in LEVF > 40%
No significant differences
No significant differe...
34
Hospitalisations for Heart Failure
ARBs vs. placebo in LEVF > 40%
Cochrane Database Syst Rev.2012 Apr 18;(4)
ARB might ...
35
Clinical effectiveness of beta-blockers in heart failure:
findings from the OPTIMIZE-HF Registry.
Am Coll Cardiol. 2009...
36
OPTIMIZE – HF: β-blockers
Hernandez AF, Hammill BG, O'Connor CM et al. J Am Coll Cardiol. 2009;53(2):184.
Reduced morta...
37
DIG trial (ancillary group): digoxin
Effects of digoxin on morbidity and mortality in diastolic heart failure:
the anci...
38
DIG trial (ancillary group): digoxin
Digoxin does not reduce morbidity or mortality in patients with
DHF and normal sin...
39
Ongoing trials
 Trial of Aldosterone Antagonist Therapy in Adults With
Preserved Ejection Fraction Congestive Heart Fa...
Case discussion
41
Back to our patient
 HF with Preserved Ejection Fraction
 Af
 HTN
42
Treatment strategy in our patient
• Reduce the congestive state
• Control HTN
• Control Af
Current medication
• Furosem...
43
Diastolic HF with chronic Af
Af Tachycardia
Shorten
diastolic
filling period
Deteriorate
HF
Rate control in DHF with Af...
44
Control Atrial Fibrillation
Current medication: Digoxin 0.125mg PO QD
Rate
control
Recommendation:
Consider beta blocke...
45
Control Atrial Fibrillation
Current medication: Digoxin 0.125mg PO QD
Rate
control
Risk of
thrombosis
Recommendation:
C...
46
 New or worse symptoms of heart failure
 Life style modification
 Low salt diet
 Medication
Breathing Weight Swelli...
47
Take home message
Treatment strategy
• Symptom reduction
• Causes and risk factors
• Possibly beneficial effect on path...
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Management of diastolic heart failure

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Management of diastolic heart failure

  1. 1. Management of Diastolic Heart Failure: What is the Recent Results in Clinical Trial 報告學生:陳秋縈 指導老師:李貽恆醫師 報告日期:2012/11/13 CASE REPORT
  2. 2. 2 Patient profile Name 吳○○ Admission date 2012/10/18 Age 79 Allergy history NKDA Gender female Social history Smoking: (-) Drinking: (-) Betel nut: (-) Drug abuse: (-) HT/BW 168cm/62.3kg BMI 22 Past history Regular medication • Hypertension • Persistent atrial fibrillation • Hyperuricemia • Impaired glucose tolerance • Amlodipine 5mg PO QD • Furosemide 20mg PO QOD • Aspirin EM 100mg PO QD • Benzbromarone 50mg PO QD Chief complaint • Productive cough and shortness of breath for 2 weeks • Mild fever up to 37.3°C in recent days
  3. 3. 3 History of present illness • Intermittent exertional dyspnea for several years • Long term follow up in local clinic 4/12 • Visit NCKUH CV OPD • Arrange further examination 4/23 • CXR: Cardiomegaly, atherosclerosis of the aorta • ECG: AF, VPC • Echocardiography: Dilated RA, LA and LVH Adequate global LV systolic performance Mild MR and TR with mild pulmonary HTN 10/18 • Suffered from productive cough and intermittent low grade fever for 2 weeks • Dyspnea, transferred to ER from OPD OPD PRESCRIPTION • Amlodipine 5mg PO QD • Furosemide 20mg PO QOD • Aspirin EM 100mg PO QDAC • Benzbromarone 50mg PO QD LOCAL CLINIC PRESCRIPTION • Olmesartan /Amodipine 20mg/5mg PO QD • Bumetanide 0.5mg QD • Digoxin 0.125mg PO QD • Aspirin EM 100mg PO QDAC • Benzbromarone 50mg PO QD
  4. 4. 4 Physical examination • VITAL SIGN TPR: 37.7/85/20 BP: 141/78 mmHg SpO2: 92% • NECK: JVE(+) • CHEST: crackles over right lower lung • HEART: irregular heart beats, grade III/IV pansystolic murmur over apex • EXT: bilateral legs pitting edema 3+ ECG • Af with RVR CXR • Cardiomegaly • Patchy consolidatoin and infiltrations over both lungs  Suspect pneumonia or lung edema
  5. 5. 5 Lab data Impression • HF with AE, favor infection induced • Af with RVR • HTN Normal range 10/18 ALBUMIN 3.5-5 4.1 g/dL CREA 0.6-1.2 1.16 mg/dL eGFR 45 ALT 0-54 15 U/L CK 30-135 154 U/L NA 135-148 145 mmol/L K 3.5-5 4.8 mmol/L GLU.P.C. 80-140 144 mg/dL CK-MB <2.9 3.62 ng/mL hsTnT 0.025 ng/mL NTproBNP <125 12956 pg/mL Normal range 10/18 WBC 3.2-9.2 9.8 10^3/μL Hb 11.6-14.8 10.8 g/dL Plt 151-366 183 10^3/μL Blast 0 % Pro 0 % Myelo 0.5 % Meta 0 % Band 1 % Seg 43-64 79.5 % Eos 0-6 0 % Baso 0-1 0 % Mono 3-9 8 % Lymph 27-47 11 % Aty-lym 0 % NRBC 0 /Count WBCs
  6. 6. 6 Hospital course Date Event Management 10/18 16:00 at ER • BT: 37.7, cough, dyspnea • CXR : patchy consolidatoins and infiltrations • WBC: 9.8 (103/μL), Seg: 79.5%, band:1% Suspect CAP • Legionella & pneumococcus Ag (urine): (-) • PCT: (-) • SOB, orthopnea • BP: 141/78 mmHg, SpO2: 92% • IRHB, JVE(+), crackles over right lower lung, lower leg pitting edema • CXR: cardiomegaly • ECG: Af with RVR • NTproBNP: 12956 pg/mL Suspect HF with AE • S/C & gram stain, B/C x 2 sets • Acetaminophen 500mg Q6HPRN if BT>38.3 • Ceftriaxone inj 1g IVD Q12H • Levofloxacin 500mg PO QDAC • O2: 3L/min • Furosemide 40mg IVP STAT • Digoxin 0.25mg in NS 50ml IVD 30min STAT
  7. 7. 7 Date Event Management 10/18 18:00 after admission HF with AE, favor infection related HTN previous under amlodipine • Scr: 1.31 mg/dL, K:4.8 mmol/L Persistent Af Gout history • Diet: 限鹽 5g/day, 限水1500ml/day • Shift amlodipine to Valsartan 80mg PO QD • Furosemide 40mg PO BID • Isosorbide DN 5mg PO TIDAC • Digoxin 0.125mg PO QD • Aspirin EM 100mg QD • Benzbromarone 50mg PO QD 10/20 • Echocardiography report  HF with Preserved Ejection Fraction (HFPEF) • SOB improved, BW↓, I/O↑ • Furosemide 40mg PO QD Hospital course Echocardiography report Dilated LA, LV, RA Adequate LV systolic performance Moderately-severe posterior-eccentric MR (3+) Moderately-severe TR (3+) Normal LV filling pressure, mean E/E'=7.7 (<8) Af with occasional VPCs LVEF: 61.1% 10/18 10/19 10/20 BW (kg) 62.3 61.25 60.8 I/O (ml) -390 -650 +40 LVEF: left ventricular ejection fraction
  8. 8. 8 Date Event Management 10/21 • Keep Valsartan use 10/22 • SOB improved, no orthopnea, less cough, less edema • F/U lab no leukocytosis WBC: 4.5 (103/μL), Seg:61.8% • CXR: complete resolution of consolidation • Valsartan 160mg PO QD • Furosemide 20mg PO QD • DC Ceftriaxone 10/23 • TPR: 36.8/60/20 • BP:113/85 mmHg • Stable condition • Discharged and OPD F/U Hospital course 10/18 10/21 Scr (mg/dL) 1.16 0.82 K (mmol/L) 4.8 3.6 10/18 10/22 Discharge Order • Valsartan 160mg PO QD • Furosemide 20mg PO QD • Isosorbide DN 5mg PO TIDAC • Digoxin 0.125mg PO QD • Aspirin EM 100mg PO QDAC • Benzbromarone 50mg PO QD • Levofloxacin 500mg PO QDAC x 4days
  9. 9. 9 Summary of our patient Drug 10/18 10/19 10/20 10/21 10/22 10/23 discharge order CAP Ceftriaxone 100mg IVD q12h Levofloxacin 500mg qdAC Acetaminophen 500mg q6h prn HF Isosorbide DN 5mg tidAC Valsartan 80mg qd 160mg QD Furosemide 40mg bid 40mg QD 20mg QD Af Digoxin 0.125mg qd Aspirin EM 100mg qd Hyperu- ricemia Benzbromarone 50mg qd BW(kg) 62.3 61.25 60.8 60.5 60.4 59.7 I/O (ml) -390 -650 +40 +450 Scr 1.16 mg/dL K 4.8 mmol/L Scr 0.82 mg/dL K 3.6 mmol/L
  10. 10. 10 Outline  Diastolic heart failure (DHF)  Definition and diagnosis criteria  Epidemiology  Pathophysiology  Clinical Manifestations  Management  Recent results in clinical trials  Case discussion  Take home message
  11. 11. 11 Heart failure  A complex clinical syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the ventricle to fill with or eject blood.  Systolic heart failure  Diastolic heart failure ACC/AHA Practice Guidelines
  12. 12. Diastolic Heart Failure (DHF) Also called: • Diastolic dysfunction • Heart failure with preserved ejection fraction (HFPEF) • Heart failure with normal ejection fraction (HFNEF)
  13. 13. 13 Definition  Vary with no global consensus  A clinical syndrome  Signs or symptoms of heart failure  Congestion, low perfusion  Normal or near normal left ventricular systolic function  Variably defined as an LVEF >40%, >45%, or >50%  Evidence of diastolic dysfunction  Abnormal left ventricular relaxation, impaired filling , myocardium stiffness 1. Galderisi M. Cardiovasc Ultrasound. 2005 Apr 4;3:9. 2. Aurigemma GP, Gaasch WH. N Engl J Med. 2004;351(11):1097. LVEF: left ventricular ejection fraction
  14. 14. 14 Diagnostic Criteria Adapted from Yturralde FR. Prog Cardiovasc Dis 2005;47:314-19 2009 Focused Update: ACCF/AHA Heart FailureGuidelines Clinical evidence of HF: Clear clinical presentation of HF or Framingham or Boston criteria If uncertain: Plasma BNP or NT-proBNP or chest x-ray or cardiopulmonary exercise testing LVEF < 50% LVEF ≥ 50% Supportive evidence: • Eccentric LVH or remodeling Supportive evidence: • Concentric LVH or remodeling • Left atrial enlargement in absence of AF • Echo Doppler or catheter evidence of diastolic dysfunction Exclusions: • Non-myocardial disease Exclusions: • Non-myocardial disease Diastolic HFSystolic HF
  15. 15. 15 Epidemiology  50% of patients with HF has normal LVEF  Increasing prevalence Secular Trends in the Prevalence of HF-PEF Owan T, et al. NEJM. 2006;355:251-9 DHF SHF
  16. 16. 16 Mortality: SHF vs. DHF  Varies with cohort studied  Differences in definition used to diagnose, co-morbidities present, composition of the populations studied Bhatia RS. NEJM. 2006;355:260-9 Owan T, et al. NEJM. 2006;355:251-9 HR 1.13; 95%CI 0.94-1.36; P=0.18 No significant difference
  17. 17. 17 Patient Characteristics: SHF vs. DHF Owan T, et al. NEJM. 2006;355:251-9 older female      lower SHF DHF
  18. 18. 18 Etiology Major causes  Hypertension  Coronary heart disease  Diabetes  Cardiomyopathy Precipitating factors  Excess salt intake  Exercise  Anemia  Infection  Tachycardia  Arrhythmia
  19. 19. 19 Pathophysiology Mandinov L, Eberli FR, Seiler C, Hess OM. Cardiovasc Res. 2000 Mar;45(4):813-25. Abnormalities of active relaxation Passive stiffness of myocardium Impaired Left ventricular filling capacity Risk factors HTN, CAD, DM, Cardiomyopathy, Obesity, Aging
  20. 20. 20 Clinical Manifestations Extravascular water ↑  Dyspnea  Elevated jugular venous pressure  Pulmonary rales  Edema Tissue perfusion ↓  Cool arms and legs  Sleepy, obtunded  Hypotension  Worsening renal function
  21. 21. 21 Management  Limited evidence, no standard treatment regimen Hunt, et al. 2009 ACCF/AHA Heart Failure Guidelines. Circulation. 2009;119:e391-e479 ACC/AHA HF PRACTICE GUIDELINE RECOMMENDATIONS Class Level • Control systolic and diastolic hypertension in accordance with published guidelines I A • Use diuretics to control pulmonary congestion and peripheral edema I C • Coronary revascularization in patients with CAD in whom ischemia is judged to be having adverse effect on cardiac function IIA C • In patients with atrial fibrillation − Control ventricular rate − Restoration and maintenance of sinus rhythm might improve symptoms I IIB C C • Use of beta-adrenergic blocking agents, ACEIs, ARBs, or calcium antagonists in patients controlled hypertension might be effective to minimize symptoms of HF IIB C • Usefulness of digitalis to minimize symptoms is not well established IIB C Level of Evidence C: Only consensus opinion of experts, case studies, or standard of care.
  22. 22. 22 Goal • Control hypertension • Reduce the congestive state • Treat and prevent myocardial ischemia • Maintain atrial contraction and prevent tachycardia • Promote regression of hypertrophy and fibrosis* Management Principle Target on • Symptom reduction • Causes and risk factors • Possibly beneficial effect on pathophysiology 1. Koprowski A, Gruchala M, Rynkiewicz A. Curr Opin Cardiol. 2009 Mar;24(2):161-6. 2. Aurigemma GP, Gaasch WH. N Engl J Med. 2004 Sep 9;351(11):1097-105. *thioretical benefit Pharmacotherapy • ACEI/ARB • Aldosterone antagonist • Beta blocker • CCB • Diuretic • Other: Digoxin, Statin, Vasodilator Nonpharmacologic therapy • Lifestyle modification
  23. 23. 23 SHF vs. DHF Systolic heart failure Diastolic heart failure Pathophysiology Impaired myocardial contractility Dilated heart Impaired relaxation and filling Hypertrophied heart Ejection Fraction Reduced Normal Signs and Symptoms Similar Mortality and Morbidity No significant difference BNP/NT-proBNP Levels More elevated Less elevated Patient Characteristics Prior myocardial infarction Older Woman Obesity Hypertensive Atrial fibrillation Evidence Supported Treatment Well Poor
  24. 24. What is the recent results in clinical trial
  25. 25. 25 Completed trials for HF with preserved EF Trial Drug Patient Follow-up PEP-CHF 2006 Perindopril •n=850 •EF ≥ 40% 26.2 mo VALIDD 2007 Valsartan •n=384 •EF>50% 38 wk I-PRESERVE 2008 Irbesartan •n=4128 •EF ≥ 45% 49.5 mo CHARM-Preserved 2003 Candesartan •n = 3023 •EF > 40% 36.6 mo Cochrane Syst Rev 2012 ARB •LVEF>40%, n=7151 •LVEF≤40% , n=3766 Meta analysis OPTIMIZE – HF 2009 β-blockers •n = 7154 •EF > 40% •Naïve to β-blockers Retrospective cohort DIG trial (ancillary group) 2006 Digoxin •N= 988 •EF > 45% 37 mo 1. Eur Heart J. 2006 Oct;27(19):2338-45 2. Lancet 2007; 369:2079. 3. N Engl J Med. 2008 Dec 4;359(23):2456-67 1. Lancet. 2003 Sep 6;362(9386):777-81 2. Cochrane Database Syst Rev.2012 Apr 18;(4) 3. J Am Coll Cardiol. 2009;53(2):184 4. Lancet. 2003 Sep 6;362(9386):777-81
  26. 26. 26 PEP-CHF: Perindopril Perindopril in Elderly People with Chronic Heart Failure Eur Heart J. 2006 Oct;27(19):2338-45 Patient N=850, age≥ 70y (median age 75 y) with diastolic dysfunction, exclude LVEF < 40% hospitalized for a cardiovascular cause within previous 6mo Intervention Perindopril titrate to 4mg QD vs. Placebo Outcome Primary: All-cause mortality or hospitalization for HF Follow-up mean 26.2 mo (range 12-30) Cleland JG, Tendera M, Adamus J, et al. Eur Heart J. 2006 Oct;27(19):2338-45. ACEI
  27. 27. 27 PEP-CHF: Perindopril Cleland JG, Tendera M, Adamus J, et al. Eur Heart J. 2006 Oct;27(19):2338-45. Results Perindopril vs. Placebo •Reduce unplanned heart failure related hospitalization at 1 year 8% vs. 12.4% (p = 0.033, NNT 23) •All-cause mortality or hospitalization for HF 23.6% vs. 25.1% (HR 0.92; 95% CI 0.70 to 1.21; p = 0.545)
  28. 28. 28 VALIDD (Valsartan in Diastolic Dysfunction) Effect of angiotensin receptor blockade and antihypertensive drugs on diastolic function in patients with hypertension and diastolic dysfunction: a randomised trial. Lancet. 2007 Jun 23;369(9579):2079-87 Patient n = 384, History of stage 1 or 2 essential HTN, LVEF>50% Give antihypertensive agents not inhibit RAA system (diuretic, βb, ccb, α blocker) BP target under 135/80mmHg Intervention Valsartan titrate to 320mg/day vs. Placebo Outcome Change in diastolic relaxation velocity Change in BP Follow-up 38 wk Results Valsartan vs. Placebo •Reduce BP and increase diastolic relaxation velocity not significant between groups significantly from baseline(p<0.0001)  Valsartan may not improve diastolic function beyond antihypertensive effect Lowering BP improves diastolic function irrespective of the type of antihypertensive agent used Solomon SD, Janardhanan R, Verma A, et al. Lancet. 2007 Jun 23;369(9579):2079-87 ARB
  29. 29. 29 I-PRESERVE: Irbesartan Irbesartan in patients with heart failure and preserved ejection fraction N Engl J Med. 2008 Dec 4;359(23):2456-67 Patient n = 4128, mean age 72 y EF ≥ 45% NYHA class II-IV symptoms Hospitalized for HF during last 6 mo or persist class III or IV symptoms Intervention Irbesartan titrate to 300mg/day vs. Placebo Mean dose 275mg/day Outcome Primary: All-cause death or hospitalization for a cardiovascular cause Follow-up mean 49.5 mo Results Irbesartan vs. Placebo •36% vs. 37% (HR 0.95; 95% CI 0.86 to 1.05; p = 0.35) No significant differences between groups  Irbesartan does not reduce mortality or hospitalization in HFPEF Massie BM, Carson PE, McMurray JJ, et al. N Engl J Med. 2008 Dec 4;359(23):2456-67 ARB
  30. 30. 30 CHARM-Preserved: Candesartan Effects of candesartan in patients with chronic heart failure and preserved left- ventricular ejection fraction: the CHARM-Preserved Trial Lancet. 2003 Sep 6;362(9386):777-81 Patient n = 3023, mean age 67 y EF > 40% NYHA class II-IV for at least 4 wks hospital admission for cardiovascular causes Intervention Candesartan titrate to 32mg/day vs. Placebo Mean dose at 6 mo: 25mg/day Outcome Primary: cardiovascular death or hospital admission for HF Follow-up mean 36.6 mo Yusuf S, Pfeffer MA, Swedberg K, et al. Lancet. 2003 Sep 6;362(9386):777-81. ARB
  31. 31. 31 Results Candesartan vs. Placebo •Reduce hospital admission for HF 15.9% vs. 18.3% (p=0.047, NNT 42) •Cardiovascular death or hospital admission for HF 22% vs. 24% (adjusted HR 0.86; 95% CI 0.74 to 1.00; p = 0.051) CHARM-Preserved: Candesartan Yusuf S, Pfeffer MA, Swedberg K, et al. Lancet. 2003 Sep 6;362(9386):777-81 ARB
  32. 32. 32 Angiotensin receptor blockers for heart failure Cochrane Database Syst Rev. 2012 Apr 18;4:CD003040.  Study design: Systemic review of RCTs  Objective: Compare ARBs with ACEIs or placebo on mortality, morbidity and withdrawals due to adverse effects in patients with symptomatic HF (NYHA Class II to IV) (subgroup: LVEF>40%, LVEF≤40% )  Results: 11 trials with 11,794 patients compared ARBs vs. placebo 2 trials in 7,151 patients with LVEF > 40% included  Candesartan (CHARM-preserved trial)  Irbesartan (I-PRESERVE trial) ARB
  33. 33. 33 Total Mortality Total Hospitalizations ARBs vs. placebo in LEVF > 40% No significant differences No significant differences Cochrane Database Syst Rev.2012 Apr 18;(4) ARB
  34. 34. 34 Hospitalisations for Heart Failure ARBs vs. placebo in LEVF > 40% Cochrane Database Syst Rev.2012 Apr 18;(4) ARB might reduce hospitalization for heart failure but not total hospitalizations or mortality in patients with symptomatic HF and EF > 40% ARB
  35. 35. 35 Clinical effectiveness of beta-blockers in heart failure: findings from the OPTIMIZE-HF Registry. Am Coll Cardiol. 2009;53(2):184 Study design A retrospective cohort study Objective Examine associations between initiation of β-blocker therapy and outcomes Data source OPTIMIZE-HF(Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients With Heart Failure) Centers for Medicare and Medicaid Services (CMS) Patient N= 7154 (LVSD: 3001; preserved systolic function: 4153), age>65y hospitalized with HF Naïve to β-blockers Intervention newly initiated β-blocker vs. no β-blocker Outcome Mortality, rehospitalization, and a combined mortality–rehospitalization OPTIMIZE – HF: β-blockers Hernandez AF, Hammill BG, O'Connor CM et al. J Am Coll Cardiol. 2009;53(2):184. β-blockers
  36. 36. 36 OPTIMIZE – HF: β-blockers Hernandez AF, Hammill BG, O'Connor CM et al. J Am Coll Cardiol. 2009;53(2):184. Reduced mortality and rehospitalization rates No improvement in mortality or rehospitalization β-blockers SHF DHF
  37. 37. 37 DIG trial (ancillary group): digoxin Effects of digoxin on morbidity and mortality in diastolic heart failure: the ancillary digitalis investigation group trial. Circulation. 2006;114(5):397 Patient n = 988, mean age 67 y EF > 45% NYHA class I-IV Normal sinus rhythm Most patient were taking ACEI and diuretics Intervention Digoxin 0.125, 0.25, 0.375, or 0.5 mg/day vs. Placebo (n= 496) Mean dose: 0.25mg/day Outcome HF hospitalization or HF mortality Follow-up mean 37 mo Results Digoxin vs. Placebo •HF hospitalization or HF mortality 21% vs. 24% (HR 0.82; 95% CI 0.63 to 1.07; p = 0.136) Yusuf S, Pfeffer MA, Swedberg K, et al. Lancet. 2003 Sep 6;362(9386):777-81. Digoxin
  38. 38. 38 DIG trial (ancillary group): digoxin Digoxin does not reduce morbidity or mortality in patients with DHF and normal sinus rhythm receiving ACEI and diuretics Digoxin
  39. 39. 39 Ongoing trials  Trial of Aldosterone Antagonist Therapy in Adults With Preserved Ejection Fraction Congestive Heart Failure (TOPCAT) Start Date: August 2006 Estimated Completion Date: July 2013 N = 4500  Study design: Randomised Double blind clinical trial  Compare: Spironolactone vs. placebo  Primary outcome: hospitalization for the management of heart failure and Aborted cardiac arrest ClinicalTrials.gov: NCT00094302 Spironolactone
  40. 40. Case discussion
  41. 41. 41 Back to our patient  HF with Preserved Ejection Fraction  Af  HTN
  42. 42. 42 Treatment strategy in our patient • Reduce the congestive state • Control HTN • Control Af Current medication • Furosemide 20mg PO QD • Isosorbide DN 5mg PO TIDAC • Valsartan 160mg PO QD • Aspirin EM 100mg PO QDAC • Digoxin 0.125mg PO QD Target on • Symptom reduction • Causes and risk factors • Possibly beneficial effect on pathophysiology
  43. 43. 43 Diastolic HF with chronic Af Af Tachycardia Shorten diastolic filling period Deteriorate HF Rate control in DHF with Af is important!  LV filling in DHF  Occurs largely in late diastole  More dependent on atrial contraction
  44. 44. 44 Control Atrial Fibrillation Current medication: Digoxin 0.125mg PO QD Rate control Recommendation: Consider beta blocker after the patient is stable Start at low dose then titrate as tolerated Drug of choice mg/tab Initial dose Max dose Bisoprolol 5 1.25 mg QD 10 mg QD Metoprolol SR 100 12.5-25 mg QD 200 mg QD Carvedilol 6.25 25 3.125 mg BID 25 mg BID Potential beneficial effect • Heart rate • Myocardial oxygen demand  • Blood pressure  -promote regression of LVH
  45. 45. 45 Control Atrial Fibrillation Current medication: Digoxin 0.125mg PO QD Rate control Risk of thrombosis Recommendation: Consider beta blocker after the patient is stable Start at low dose then titrate as tolerated Recommendation: CHADS2= 3 Suggest warfarin use Current medication: Aspirin EM 100mg PO QD Score C CHF 1 H HTN 1 A Age ≥75 yrs 1 D DM 1 S2 Stroke or TIA 2
  46. 46. 46  New or worse symptoms of heart failure  Life style modification  Low salt diet  Medication Breathing Weight Swelling Activity Patient education
  47. 47. 47 Take home message Treatment strategy • Symptom reduction • Causes and risk factors • Possibly beneficial effect on pathophysiology  Control : BP, HR, congestive state, myocardial ischemia Diastolic heart failure • Signs or symptoms of heart failure  Similar with SHF • Normal or near normal left ventricular systolic function  LVEF ≥ 50% • Evidence of diastolic dysfunction  Abnormal relaxation, myocardium stiffness, impaired filling
  48. 48. THANKS

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